DESCRIPTION (Taken from the applicant's Abstract) Insulin-like growth factor-II (IGF-II) is thought to play an important role in fetal and placental development. The most compelling evidence concerning the role of IGF-II comes from transgenic mice whose IGF-II gene was inactivated by targeted mutagenesis (null mice). The phenotype of the IGF-II null mice is growth retardation of both fetus and placenta during the last two-thirds of gestation. In recent studies I compared the placentas of IGF-II null and normal mice and found that there were fewer glycogen cells present in the null placentas when compared to normal controls, suggesting that the glycogen cells do not efficiently differentiate in the absence of IGF-II. In addition, glycogen content of the placenta and fetal liver was greatly reduced in the null mouse suggesting that IGF-II may play important roles in glucose transport and glycogen synthesis, similar to those regulated by insulin in later postnatal life. The overall goal of this proposal is to determine the function of IGF-II in the placenta and the mechanism(s) by which this hormone may be affecting placental and fetal growth. The IGF-II null mouse will be used to: 1) determine the biochemical basis for reduced glycogen content in the IGF-II null placenta, as well as its functional consequences of reduced glycogen content, 2) examine whether IGF-II can correct the defects in glycogen cell differentiation and placental glycogen content, and 3) determine whether other factors, such as varying glucose levels, can affect placental and hepatic glycogen content and thereby influence fetal and placental size in the IGF-II deficient mice. These studies should clarify the relationships among IGF-II, placental and fetal carbohydrate metabolism, and their impact on perinatal growth.